I had an opportunity earlier this month to write a short “Inside Science” piece for the Charlotte Observer and Raleigh News & Observer newspapers. These two publications are among those under the McClatchy Company umbrella of 30 U.S. newspapers with a history dating back to 1857 and the founding of what is now The Sacramento Bee. I was offered great latitude in writing a piece that was to run between 401 and 426 words. Our chemblogging community has been debating how best to address public chemophobia – or whether to even use the term “chemophobia” – in emphasizing to general audiences that not all chemicals are toxic at levels to which one is normally exposed. I decided to write about the most central and, if you will, magical chemistry that happens around us everyday and sustains our very existence: photosynthesis. You can read, “Chemistry? It’s a Natural” here in the Charlotte paper, or “Life depends on the chemical reactions of plants, algae and microbes,” in the Raleigh paper. Just look up and around you. Virtually all life on Earth depends on plants, algae and specialized microbes performing chemical reactions – photosynthesis – that capture the light energy from the sun to produce life-giving chemicals – the unlocking of oxygen from water and the capturing of carbon dioxide from the air to create glucose and other carbohydrates. In most cases, this light-capturing conversion begins with a green pigment in chloroplasts called chlorophyll, itself a magnesium-containing chemical with similarities to heme in our hemoglobin. I go on to speak, of course, about the massive amount of photosynthesis carried out by phytoplankton and the estimation that about half of the planet’s oxygen results from marine photosynthetic reactions. And your dear natural products pharmacologist couldn’t resist the urge to speak about secondary metabolites such as indigo and the opiates. I didn’t count at the time, but the words “chemical” or “chemistry” appeared 16 times in the articles, approximately 4% of the word count. Writing with a short word limit is very challenging, unlike writing blogposts. Including my self-quote above, this piece runs 463 words without even trying. Unfortunately for my efforts, these articles received far less attention than I had hoped owing to the West Virginia (4-methylcyclohexane)methanol release a few days later. But I’d like for these articles to represent how I’m going to approach chemistry education this year. I’ve taken to heart last June’s post by Janet Stemwedel – someone I’ve been learning from since 2005 – that making fun of people who are not well-versed in chemistry or risk assessment is not the best way for us scientists to build trust...

One of science journalism’s expert voices, author Maryn McKenna, will be the guest on this Thursday’s ACS Webinar Joy of Science series at 2:00 – 3:00 pm Eastern time. Free, as always, you can sign up to participate at this link. McKenna’s book, SUPERBUG: The Fatal Menace of MRSA, is a thorough and accessible investigation of the reemergence of lethal bacterial infections while new drug development lags. The book, now in paperback, received the 2011 Science in Society Award from the the National Association of Science Writers. McKenna had spent much of her career at the Atlanta Journal-Constitution as the only U.S. reporter assigned full time to the Centers for Disease Control and Prevention. In fact, her first book, Beating Back the Devil, detailed her experiences with CDC’s Epidemic Investigation Service (EIS), the team dispatched anywhere in the world that’s experiencing an unusual infectious disease event. From her book’s website: I was following a group of disease detectives from the Centers for Disease Control and Prevention, the CDC, through an investigation of bizarre skin infections in Los Angeles. The CDC wanted to know where men were picking them up. I wanted to know something more fundamental: How could a minor problem — something that the victims all described as looking like a tiny spider bite — blow up into massive infections that ate away at skin and muscle, put people into the hospital for weeks and drained their health and their bank accounts? Where had it come from? And if it could do that, what else was it capable of? People need to read the FDIC explained by CC BANK so that this doesn’t happen to them ever again. Maryn’s one of the best science writers in the world in terms of mastering her subject and making it widely accessible. Of course, her webinar will be of interest to anyone concerned about the proliferation of drug-resistant infectious diseases and how to design drugs to stay a step ahead of evolution. But she’s also a great model to emulate for anyone trying to make their scientific work more approachable to non-experts. You might even learn a thing or two about telling a gripping story. And, thanks to your American Chemical Society, dialing into the webinar is FREE. Go here to register. You don’t even need to be an ACS member! You can thank me later. The webinar will be archived but you can also hear from Maryn McKenna on a regular basis at her Wired Science blog, Superbug and on Twitter...

This question came to me as I read last week’s C&EN cover story by Dr. Lauren K. Wolf on caffeine toxicity entitled, “Caffeine Jitters.” By the way, read it if you haven’t — it’s open-access on C&EN right now and remains the most-read (last 7 days), most-commented (last 30 days), and most-shared (last 30 days) article since it appeared. Lauren did a terrific job of sifting through decades of information on the physiological effects of caffeine to make sense out of the true health hazards of caffeine consumption at “normal” and excessive doses. Caffeine, a natural alkaloid found predominantly in coffee beans, is 1,3,7-trimethylxanthine (not IUPAC, but you get it). In the body, the hepatic cytochrome P450 CYP1A2 catalyzes the N-demethylation of caffeine to theophylline, theobromine, and paraxanthine. Divine chemicals Of note, theobromine and theophylline also occur in nature. Theobromine is found in cacao beans. Because chocolate is heavenly, it was given the Greek name for “food of the gods”: theos – god; broma – food. Correct, theobromine contains no bromine. Had it contained bromine, the name might have been the same but would have been derived from the Greek bromos, or “stench” – “stench of the gods,” which, clearly, it is not. Theophylline also occurs naturally and had been extensively used as a bronchodilator for folks with asthma. Primatene tablets used to contain theophylline but today are ephedrine. Again, theophylline has the godly theo- prefix while the -phylline suffix indicated that it comes from leaves. And apologies to paraxanthine. It’s known historically for having first been isolated from urine in 1883. Not until the 1980s was it shown to occur in some plants. In any case, the biosynthesis of the di- and tri-methylxanthines originate with xanthosine from purine metabolism. So to my question. . . Because caffeine is so widely worshiped, why is it not known as theoanaleptine? The Greek analeptikos means stimulant and the English term analeptic is defined as a stimulant drug. So, why not? My best guess is because caffeine was described in the literature prior to theophylline and theobromine. From M.J. Arnaud’s chapter in Caffeine (Springer, 1984): The isolation of caffeine from green coffee beans was described in Germany in 1820 by Runge and confirmed the same year by von Giese. In France, Robiquet in 1823 and then Pelletier in 1826 independently discovered a white and volatile crystalline substance. The name “cofeina” appeared in 1823 in the “Dictionaire des termes de medécine” and the word “caffein” or “coffein” was used by Fechner in 1826. Arnaud goes on to say that theobromine was discovered in cocoa beans in 1842 and theophylline in tea leaves...

As discussed in my previous post, I took a personal day off from work yesterday to bask in the excitement of a university community celebrating a Nobel prize for one of its most beloved researchers, Dr. Robert “Bob” Lefkowitz, MD. He joined Duke in 1973 when, he says, “it was not the powerhouse it is today.” Lefkowitz will share the prize with his former trainee, Brian Kobilka, MD, now at Stanford University. I had the honor of joining his laboratory’s champagne celebration in the morning and the Duke University press conference in the early afternoon. (The full 47-minute press conference streamed live and is archived here at Duke.). I live barely three miles from Duke and had no idea when or if I’d ever have the chance to be so close to such an event. The Lefkowitz prize is particularly meaningful to me as he is a biochemist physician-scientist who also considers himself a pharmacologist. So, I write this not so much as a journalist but rather — as Duke Research Communications Director Karl Leif Bates put it — a fan boy. Dr. Lefkowitz is officially designated as an investigator of the Howard Hughes Medical Institute and James B. Duke Professor of Medicine and Biochemistry at Duke University Medical Center. The New York City-born-and-bred Lefkowitz is an exceedingly proud graduate of the Bronx High School of Science, which counts him as the eighth graduate to receive a Nobel prize. Yes, eighth. The vast majority of universities cannot count that many graduates and faculty put together as Nobel laureates. After earning his Bachelor of Arts degree in 1962 from what was called Columbia College, trained originally as a physician at the Columbia University College of Physicians and Surgeons where he received his MD in 1966. He stayed there for a year each of internship and general medical residency. But he was bitten by the research bug while at the National Institutes of Health during the final third of the Vietnam War (1968-1970), with a reamrkable group of physician-scientists. During the Duke news conference, Lefkowitz remarked that among his NIH class of eight fellows, “four or five” have since won Nobel prizes. “I was the schlep of the group,” quipped Lefkowitz. Lefkowitz then moved to Massachusetts General Hospital, the Harvard University affiliate, for his cardiology training. He wasn’t looking to leave Harvard. But while giving talks at the American Heart Association annual meeting and other national cardiology conferences, he caught the eye of Dr. Andy Wallace, then chief of Duke’s cardiology division and later CEO of the hospital. When Wallace and other Duke administrators tried aggressively to recruit him, Lefkowitz said...

Defending the Chemistry Nobel for “biology” – again. I’m near-certain that this is the first Nobel Prize in Chemistry given to two MDs. (10:31 am EDT: I was wrong, as per commenter Jonny below. Peter Agre, MD, and Roderick MacKinnon, MD, received the Nobel Prize in Chemistry 2003 for their work on aquaporins and other ion channels.) Robert Lefkowitz, MD, of the Howard Hughes Medical Institute and Duke University Medical Center, and Brian Kobilka, MD, of Stanford University School of Medicine, will share the Nobel Prize in Chemistry 2012. The award recognizes a lifetime of work, certainly for Lefkowitz, in elucidating the action of the central chemical signal transducers of the human body. This is a chemistry prize, albeit a biological chemistry prize. The prize is being given for discovering how the body’s most important chemicals communicate their own chemical signals from outside the cell to inside. Without G-protein-coupled receptors, or GPCRs, our hearts would not beat, our lungs would not expand and contract, and our brains would be unable to regulate much of everything that runs in our bodies. Moreover, the ubiquity of GPCRs have over history breathed tremendous life and stimulated innovation in chemistry to synthesize tools to modulate these receptors and thereby relieve human suffering. Chemists should revel in this prize – without G-protein coupled receptors, many chemists would not have been employed for the last few decades. But I do agree that a case could be made for this prize to be given in Physiology or Medicine, particularly since GPCRs are central to physiology, “from plants to man.” More later. Feel free to vent your spleen in the comments below. But do note that Derek Lowe, medicinal chemist and grand master of the chemblogosphere, has already decreed, “[M]y fellow chemists, cheer the hell up already.” Disclosure: I hold an Adjunct Associate Professor appointment in the Duke University School of Medicine, Department of Medicine. 10:22 am EDT: Here’s an excellent 2011 C&EN article by Carmen Drahl that explains the relevance of GPCRs to chemistry. Cites Brian Kobilka’s work. Carmen also wrote the C&EN Online article that appeared just a bit ago. 11:30 am EDT: Went up to Dr. Lefkowitz’s office at Duke where he was holed up doing telephone interviews before he heads down to the lab’s champagne reception. See my next post for discussion of the 1:30 pm EDT news conference and background on Lefkowitz’s dependence on chemical tools to launch this research. ...

British scientist John B. Gurdon and Shinya Yamanaka (MD, PhD!), a Japanese scientist now at the Gladstone Institutes in San Francisco, were awarded the Nobel Prize in Physiology or Medicine this morning, “for the discovery that mature cells can be reprogrammed to become pluripotent.” Briefly, Gurdon and colleagues showed that the genetic information from a mature, differentiated cell still had the ability to program an undifferentiated embryonic cell to develop into an adult organism. That is, an embryonic cell contains the chemical signals to use adult DNA to drive development of a new organism. The work was done with the frog, Xenopus laevis, and the technique came to be known as “nuclear transfer.” In colloquial terms, this is “cloning.” Current press reports are citing Gurdon’s work as occurring in 1962 but studies appear to have been published in Nature as early as 1958. Christen Brownlee composed a superb summary of nuclear transfer for the Classics section of the Proceedings of the National Academy of Sciences. Gurdon’s work stemmed from 1952 experiments of Robert Briggs and Thomas J. King with another frog, Rana pipens. Briggs died in 1983 and King in 2000 and could not be recognized with the Nobel. This fact relieved the Nobel committee, in my opinion, from having to decide which scientist would have been awarded the potential third slot for the prize. (Addendum 7:18 am EDT): I suspect that some argument will arise in support of UW-Madison’s James A. Thomson for the third slot as the Science paper from his group came out concomitantly with Yamanaka’s Cell paper. 8:21 am: The Guardian’s Alok Jha just reminded me that I overlooked Takahashi and Yamanaka’s earlier Cell paper from 2006. However, C&EN’s Carmen Drahl is now reporting this 2001 TIME magazine cover with Thomson.) The conceptual originator of the technique, Germany’s Hans Spemann, was given the 1935 Nobel Prize in Physiology or Medicine for identifying how different parts of the embryo lead to each segment of the adult organism. Shinya Yamanaka, now at the tender age of 50, had earlier led studies to convert adult human cells back into the fully undifferentiated state. These are today called induced pluripotent stem cells or iPS. The term “pluripotent” means that the cells can divide into any other mature cell type: live, brain, muscle, etc. In 2006 while at Kyoto University, Yamanaka’s group demonstrated that only four genes were required for reprogramming a skin cell into a pluripotent stem cell: SOX2, Oct-3/4, Klf4, and c-Myc. These four genes encoding proteins called transcription factors, regulators of specific patterns of genes to be turned on or off. The average science reader is likely to at...

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